Project description:In recent years, the gut microbiota and derived metabolites have emerged as relevant players in modulating several brain functions, including energy balance control. This form of distant communication mirrors that of metabolic hormones (e.g., leptin, ghrelin), that convey information about the organism's energy status by exerting effects on diverse brain regions including the master homeostatic centre the hypothalamus. However, whether the hypothalamus is also able to influence gut microbiota composition remains enigmatic. Here, we present a proof-of-concept study designed to unravel this challenging question. To this aim, we employed chemogenetics (to selectively activate or inhibit the activity of hypothalamic POMC or AgRP neurons) or administered leptin or ghrelin centrally to mice. Subsequently, we conducted microbiota composition analysis throughout the gut using 16S rRNA gene sequencing. Our results showed that these brain interventions significantly changed the gut microbiota in an anatomical and short-term (2-4h) fashion. Transcriptomic analysis indicated that these changes were associated with the reconfiguration of neuronal and synaptic pathways in the duodenum concomitant with increased sympathetic tone. Interestingly, diet-induced obesity attenuated brain-mediated changes induced by leptin in gut microbiota communities and sympathetic activation. Our findings reveal a novel and unanticipated brain-to-gut axis that acutely attunes microbiota composition at fast timescales, with potential implications for meal-to-meal adjustments and systemic energy balance control.
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as Crohn’s disease and colorectal cancer. Our data showed that Nod2-mediated risk of intestinal inflammation in colitis model is communicable to WT mice by cohousing. Here, we investigated if Nod2-deficient mice microbiota is able to change transcript profiles in Nod2-immunocompetent mice (C57Bl6/J mice) independently of colitis. Analysis used RNA extracted from colonic mucosa of C57Bl/6J mice co-housed with Nod2-deficient mice and C57Bl/6J mice alone. Direct comparisons of 4 biologicals replicates of C57Bl/6J mice cohoused with Nod2-deficient mice vs C57Bl/6J mice were performed.
Project description:A study aiming to determine if mice humanized by different donors have different gut microbiota and colonic gene expression patterns in response to the administration of a commonly prescribed, broad-spectrum antibiotic (co-amoxiclav). Male, germ-free mice were humanized by one of two healthy, unrelated human donors. 56 days later, gut microbiota and colonic transcriptome samples were analyzed at baseline, by 454 pyrosequencing and Agilent microarray, respectively. Antibiotics were then administered for 7 days, following by repeated sampling of both the microbiota and colonic RNA at days 8, 11 and 18. Results of the microbiota analysis revealed marked shifts in the composition of one donor group in response to antibiotics and not the other donor group. Transcriptomics revealed a more conserved response, however the magnitude of the effect was greater in the donor group that had a greater shift in the microbiota.
Project description:Human diet emerges as a pivotal determinant of gut microbiota composition and function. Identification of the bacterial taxa targeted by diet derived factors with causal beneficial rather than detrimental effects on therapy and their mechanism of action is challenging but necessary for future clinical progress. The germ free mice colonized with human gut bacteria and four-plants derived nanoparticles uptaking bacteria were sorted with flow cytometry and identified with 16s rRNA next-generation sequencing.
Project description:Antibiotics have long-lasting consequences on the gut microbiota with the potential to impact host physiology and health. However, little is known about the transgenerational impact of an antibiotic-perturbed microbiota. Here we demonstrated that adult pregnant female mice inoculated with a gut microbial community shaped by antibiotic exposure passed on their dysbiotic microbiota to their offspring. This dysbiotic microbiota remained distinct from controls for at least 5 months in the offspring without any continued exposure to antibiotics. By using IL-10 deficient mice, which are genetically susceptible to colitis, we showed mice that received an antibiotic-perturbed gut microbiota from their mothers had increased risk of colitis. Taken together, our findings indicate that the consequences of antibiotic exposure affecting the gut microbiota can extend to a second generation.
Project description:This study aimed to analyze changes in gut microbiota composition in mice after transplantation of fecal microbiota (FMT, N = 6) from the feces of NSCLC patients by analyzing fecal content using 16S rRNA sequencing, 10 days after transplantation. Specific-pathogen-free (SPF) mice were used for each experiments (N=4) as controls.